The present invention concerns with a novel labelled vitamin D.sub.3 derivative represented by the formula (I): ##STR1## wherein R.sup.1 represents a deuterium atom or a tritium atom, R.sup.2, R.sup.3, and R.sup.4 independently represent a hydrogen atom or a hydroxy group and R.sup.5 and R.sup.6 represent respectively a methyl group, a hydroxymethyl group or a trifluorocarbon group, as well as a production process thereof.
Vitamin D.sub.3 (hereinafter referred to as "VD.sub.3 ") derivatives have been used as therapeutical medicines for various diseases of bone such as osteoporosis and it is essential to recognize pharmacodynamics of VD.sub.3 derivatives in a living body in order to evaluate their therapeutical effect and safety, as well as to increase an efficiency of the therapy. For this purpose, it is necessary to introduce radioactive isotopes to the VD.sub.3 derivatives by using a chemical or biological method and label the derivatives.
Responding to such requirement, VD.sub.3 derivatives labelled with radioactive isotopes at a side chain by means of a biochemical method have been used so far. [Refer to H. F. DeLuca et al., Journal of Biological Chemistry; vol. 251, p. 397-402(1976)].
However, since the labelled VD.sub.3 derivatives used so far are labelled at side chains and such side chains are prone to be metabolized in vivo metabolism, there has been a fundamental problem that when the labelled VD.sub.3 derivative is administered to a living body, i.e., the labelled side chain is easily removed from its skeleton portion under the effect of in vivo metabolism. Therefore, there has been no remarkable progress in the field to compare the efficacies among various kinds of VD.sub.3 derivatives and to acquire the features of the individual VD.sub.3 derivatives.
The present inventors have studied extensively to overcome the above drawbacks and, as a result, have completed the present invention based on the finding that a VD.sub.3 derivative having a radio isotope at the skeleton portion can possess a stable labelled performance in a living body and have established a novel process to produce the labelled derivatives.